1. Field of the Invention
The present invention relates to a new polyvinyl alcohol, a gel base material and a gel, both containing the polyvinyl alcohol, and a wound dressing material primarily comprising the gel.
2. Description of the Prior Art
Gels, particularly polymer hydrogels containing water as the medium, have been conventionally used in practice in a wide variety of fields. In the food field in particular, use has been made of a variety of gel base materials comprising natural polymers, such as agar, gelatin, konjakmannan and the like; and foodstuffs of hydrogels comprising these gel base materials have been commonly used.
Recently, the development of application techniques of versatile gel functions has made progress in a wider field, and, accordingly, the field of gel application has been enlarged steadily. For example, the development of highly biocompatible gels has been remarkable, including the development of highly water-absorbable gels used in products such as disposable diapers and hygienic napkins, gels to immobilize enzymes and bacteria, contact lenses, artificial muscles, artificial organs, and wound dressings.
Following the progress of gel basic science, represented by the discovery of the phase transition phenomenon of gels, diverse attempts have been made to apply gels to highly functional products such as sensors, functional separation membranes, release control membranes, switches, and actuators.
Polymer compounds as gel base materials can be divided into natural polymers, represented by gelatin and a variety of polysaccharides, and synthetic polymers such as polyacrylic acid, poly(2-hydroxyethyl methacrylate), polyacrylamide, and polyvinyl alcohol. However, recent innovative gel applications have demanded base materials with flexibility, transparency, resistance to moist heat and resistance to hot water, making the development of a polymer base material capable of forming such a gel desirable.
As noted above, one important gel application is in wound dressing materials. It is generally required that wound dressing materials should occlusively hold a variety of healing-promoting growth factors contained in the wound exudate onto the wound to promote healing. Gauze and ointments conventionally used for treating wounds, such as lacerations, burns, ulcers and bed sores, operate by absorbing the exudate from the wound site and preventing the extraneous infiltration of bacteria and the like. It has been recently determined that a variety of growth factors (for example, bFGF, TGF .beta., etc.) that promote healing are present in the exudate from wounds see Howell, J. M., Current and Future Trends in Wound Healing, Emerg. Med. Clin. Amer., 10, 655-663 (1992), etc.!. Thus, attention has been focused on occlusive dressing materials exerting an effect of promoting wound healing by holding these growth factors on the wounds see Eaglestein, W. E., Experience with biosynthetic dressings, J. Am. Acad. Dermatol., 12, 434-440 (1985)!.
Such occlusive wound dressing materials include conventional materials such as polyurethane films, hydrocolloids, and non-woven fabrics comprising alginate fiber, and polyvinyl alcohol sponge, as well as hydrogels such as polyvinyl alcohol hydrogel, polyethylene glycol hydrogel, and polyacrylamide hydrogel. More specifically, various publications have proposed the following occlusive wound dressing materials;
1. a wound treating device made of a non-woven fiber fabric of a mixture of an insoluble alginate and a soluble alginate (WO 90/01954);
2. a wound dressing material produced by incorporating a hydrogel of a borate-modified gum guaiac in the pores of an open-cell foam comprising a biocompatible synthetic material, and then attaching a peptide that promotes wound healing, through a free hydroxyl group and/or an amino group and a bifunctional coupling agent, on the surface of the hydrogel, and/or making the hydrogel contain an antiseptic or anti-fungal substance (WO 92/03172);
3. a wound dressing material comprising a hydrogel formed from a polyvinyl alcohol with a saponification degree of 95 mol % or more and a viscosity average polymerization degree of 1500 or more and a water-soluble organic compound having two to eight hydroxyl groups (Japanese Patent Application Kokai (Laid-open) No. Sho 58-92359);
4. a semi-transparent, water-insoluble hydrogel in semi-crystals for use as a wound dressing material, which is produced by physically cross-linking polyvinyl alcohol and a complexing agent such as poly(methyl vinyl ether/maleic anhydride) (EP 0583170); and
5. a long active substance for use as a wound dressing material, produced by incorporating pilocarpine hydrochloride and the like in a polyvinyl alcohol hydrogel including hyaluronic acid and/or the salt thereof Japanese Patent Application Kokai (Laid-open) No. Hei 3-215417!.
Among the above-noted conventionally known wound dressing materials, wound dressing materials comprising a polyurethane film are satisfactory to some extent with respect to transparency and occlusiveness. However, due to their inability to absorb water, the polyurethane wound dressing materials cannot be applied to wounds having a lot of exudate.
Some polyethylene glycol hydrogels and polyacrylamide hydrogels are transparent. However, such gels can induce chronic inflammation due to contact with the wound. Further, the raw material monomers of these two types of gels are so highly toxic that the monomers remaining in the hydrogels or the degradation products of these gels may potentially exert their toxicity.
Although wound treating devices comprising hydrocolloids, polyvinyl alcohol sponges and non-woven fabrics of a alginate fiber mixture have the ability to retain exudate, the devices are unfortunately so opaque that wounds cannot be observed through them. Furthermore, it has been reported that the principal components of hydrocolloid wound dressing materials that remain in repaired tissues for a prolonged period can trigger chronic inflammation see Young, S. R. et al., Comparison of the Effect of Semi-occlusive Polyurethane Dressings and Hydrocolloid Dressings on Dermal Repair: 1. Cellular Changes, J. Invest. Dermatol., 97, 586-592 (1991)!.
Once bacterial infection occurs during the attachment of these wound dressing materials, the moist environment serves as such a suitable medium for bacteria that the bacteria grow rapidly to possibly develop into a severe infection.
Furthermore, in the above-noted item 2, a wound healing-promoting peptide is chemically bonded onto the surface of the wound dressing material and the chemical bonding is never broken. Therefore, the effect can be exerted only at the site in contact with the wound dressing material.
Furthermore, while the wound dressing material described above in item 3 has some degree of mechanical strength, if the material is attached onto a wound site, the site cannot be observed through the material because of its opaqueness. Additionally, the material is solubilized during a conventional steam sterilization process at a temperature of 121.degree. C. for 20 minutes. Thus, the material has such poor resistance to moist heat that it cannot be completely sterilized. Additionally, the wound dressing material is not safe since it contains high levels of solubilized matter even at a temperature at which the material itself is not solubilized.
The hydrogel described above in item 4 is semitransparent at a thickness of 1000 .mu.m or less, but the hydrogel does not have sufficient transparency that wounds can be observed through the hydrogel even at this thickness. In order to provide satisfactory water absorptivity as an occlusive wound dressing material, the hydrogel should be of a thickness above 1,000 .mu.m. In that case, however, the hydrogel turns opaque or nearly opaque, so that observation of wounds is much more difficult. Furthermore, because the completing agent is bonded to the polyvinyl alcohol by a physical cross-linking in the hydrogel, the hydrogel cannot be steam sterilized. Thus, the hydrogel cannot be sterilized completely. Additionally, the hydrogel contains high levels of solubilized matter even at low temperatures at which the hydrogel itself cannot be solubilized, and therefore, the hydrogel is of insufficient safety. Thus, the hydrogel is not suitable as a wound dressing material.
The polyvinyl alcohol hydrogel described above in item 5 may be prepared as a transparent material, depending on the production process, but the gel has poor handleability due to low physical strength. The gel, having a low cross-linking degree, cannot be steam sterilized so the gel cannot be sterilized completely. Furthermore, the hydrogel also contains high levels of solubilized matter even at a temperature at which the gel itself is not solubilized, so the gel is less safe. Additionally, when the degree of cross-linking of the hydrogel is elevated under irradiation, problems may occur, such as breaking of the main chain via radiation, decrease of the water content, decrease in flexibility and the like. Thus, the gel does not have sufficient physical properties for use as a wound dressing material.